DESCRIPTION: (Applicant's Description) The purpose of this project is to synthesize six fluorescent cobalamin derivatives and select the optimal compound for use as an improved tumor marker in the sentinel lymph node biopsy procedure for breast cancer . Our work to date has shown that all cancer and leukemia cell lines tested have an unusually high requirement for cobalamin (Vitamin B12). A fluorescent derivative of cobalamin should be a good visual marker that is specific for cancer cells and thereby aid in the visual identification of metastatic disease in lymph ducts and nodes. A fluorescent cobalamin conjugate may also improve the definition of tumor micro margins and aid in the surgical excision of cancerous tissue while sparing healthy tissue. As an intraoperative marker for metastatic breast disease, it may decrease the false-negative rate of the sentinel node biopsy procedure as it is currently practiced and provide a better quality of life for patients through the preservation of healthy breast tissue and healthy axial lymph nodes. This proposal will fund the initial evaluation of a fluorescein-cobalamin derivative we now have in hand, and fund the synthesis and evaluation of several second-generation fluorescent cobalamin conjugates that should be brighter and more photostable than our existing compound. Fluorescent cobalamin conjugates will be tested in primary human tumors that are removed from patients undergoing breast cancer operations.